Solid-Phase Synthesis of Biaryl Cyclic Peptides Containing a Histidine-Phenylalanine Linkage

The feasibility of the solid-phase intramolecular 4(5)-arylation of a histidine residue to obtain biaryl cyclic peptides bearing a His-Phe linkage was esta     

Antimicrobial and antiviral activities of an actinomycete (Streptomyces sp.) isolated from a Brazilian tropical forest soil

A promising producer of bioactive compounds isolated from a Brazilian tropical soil was tested for its range of antimicrobial activities. Strain 606, classified as Streptomyces sp., could not be identified up to species level, suggesting a possible new taxon. The supernatant and 10 extracts and fractions, obtained by extraction and chromatographic techniques, presented antimicrobial activity using antibiograms. The methanolic fraction was highly active against pathogenic bacteria, phytopathogenic fungi and the human pathogenic yeast Candida albicans. It also possessed high antiviral activity inhibiting the propagation of an acyclovir-resistant herpes simplex virus type 1 strain on HEp-2 cells at non-cytotoxic concentration. The strong cytotoxic effect suggests an antitumour action. This revised version was published online in August 2006 with corrections to the Cover Date.     

Hydrolysis of fish oil by hyperactivated rhizomucor miehei lipase immobilized by multipoint anion exchange

Rhizomucor miehei lipase (RML) is greatly hyperactivated (around 20‐ to 25‐fold toward small substrates) in the presence of sucrose laurate. Hyperactivation appears to be an intramolecular process because it is very similar for soluble enzymes and covalently immobilized derivatives. The hyperactivated enzyme was immobilized (in the presence of sucrose laurate) on cyanogen bromide‐activated Sepharose (very mild covalent immobilization through the amino terminal residue), on glyoxyl Sepharose (intense multipoint covalent immobilization through the region with the highest amount of Lys residues), and on different anion exchangers (by multipoint anionic exchange through the region with the highest density of negative charges). Covalent immobilization does not promote the fixation of the hyperactivated enzyme, but immobilization on Sepharose Q retains the hyperactivated enzyme even in the absence of a detergent. The hydrolysis of fish oils by these hyperactivated enzyme derivatives was sevenfold faster than by covalently immobilized derivatives and three and a half times faster than by the enzyme hyperactivated on octyl‐Sepharose. The open structure of the hyperactivated lipase is fairly exposed to the medium, and no steric hindrance should interfere with the hydrolysis of large substrates. These new hyperactivated derivatives seem to be more suitable for hydrolysis of oils by RML immobilized inside porous supports. In addition, the hyperactivated derivatives are fairly stable against heat and organic cosolvents. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011     

The role of nutrition on epigenetic modifications and their implications on health

Nutrition plays a key role in many aspects of health and dietary imbalances are major determinants of chronic diseases including cardiovascular disease, obesity, diabetes and cancer. Adequate nutrition is particularly essential during critical periods in early life (both pre- and postnatal). In this regard, there is extensive epidemiologic and experimental data showing that early sub-optimal nutrition can have health consequences several decades later.     

Lysosomal accumulation and recycling of lipopolysaccharide to the cell surface of murine macrophages, an in vitro and in vivo study.

In this study, we detailed in a time-dependent manner the trafficking, the recycling, and the structural fate of Brucella abortus LPS in murine peritoneal macrophages by immunofluorescence, ELISA, and biochemical analyses. The intracellular pathway of B. abortus LPS, a nonclassical endotoxin, was investigated both in vivo after LPS injection in the peritoneal cavity of mice and in vitro after LPS incubation with macrophages. We also followed LPS trafficking after infection of macrophages with B. abortus strain 19. After binding to the cell surface and internalization, Brucella LPS is routed from early endosomes to lysosomes with unusual slow kinetics. It accumulates there for at least 24 h. Later, LPS leaves lysosomes and reaches the macrophage cell surface. This recycling pathway is also observed for LPS released by Brucella S19 following in vitro infection. Indeed, by 72 h postinfection, bacteria are degraded by macrophages and LPS is located inside lysosomes dispersed at the cell periphery. From 72 h onward, LPS is gradually detected at the plasma membrane. In each case, the LPS present at the cell surface is found in large clusters with the O-chain facing the extracellular medium. Both the antigenicity and heterogenicity of the O-chain moiety are preserved during the intracellular trafficking. We demonstrate that LPS is not cleared by macrophages either in vitro or in vivo after 3 mo, exposing its immunogenic moiety toward the extracellular medium.     

The effects of insulin on choline kinase activity in cultured rat liver cells

The effect of insulin on phosphatidylcholine biosynthesis in cultured rat liver cells was assessed by measuring changes in the activity of the first enzyme in the choline pathway of phosphatidylcholine biosynthesis, choline kinase (ATP: cholinephosphortransferase, EC 2.7.1.32), in the presence or absence of the hormone. Choline kinase specific activity in liver cells incubated for 18 hours in the presence of 10^?7M insulin increased two-fold from 3.4 ± 0.3 nmoles phosphorylcholine formed/min/mg protein to 7.5 ± 0.6 nmoles/min/mg protein. This effect was dose dependent and reversed by the addition of actinomycin D and cycloheximide. It is concluded that the increase in specific activity is due to synthesis of new enzyme rather than activation of existing enzyme.     

Comparison of dose distribution in IMRT and RapidArc technique in prostate radiotherapy

AimThe aim was to provide a dosimetric comparison between IMRT and RapidArc treatment plans with RPI index with simultaneous comparison of the treatment delivery time.BackgroundIMRT and RapidArc provide highly conformal dose distribution with good sparing of normal tissues. However, a complex spatial dosimetry of IMRT and RapidArc plans hampers the evaluation and comparison between plans calculated for the two modalities. RPI was used in this paper for treatment plan comparisons. The duration of the therapeutic session in RapidArc is reported to be shorter in comparison to therapeutic time of the other dynamic techniques. For this reasons, total treatment delivery time in both techniques was compared and discussed.Materials and methods15 patients with prostate carcinoma were randomly selected for the analysis. Two competitive treatment plans using respectively the IMRT and RapidArc techniques were computed for each patient in Eclipse planning system v. 8.6.15. RPIwin^® application was used for RPI calculations for each treatment plan.Additionally, total treatment time was compared between IMRT and RapidArc plans. Total treatment time was a sum of monitor units (MU) for each treated field.ResultsThe mean values of the RPI indices were insignificantly higher for IMRT plans in comparison to rotational therapy. Comparison of the mean numbers of monitor units confirmed that the use of rotational technique instead of conventional static field IMRT can significantly reduce the treatment time.ConclusionAnalysis presented in this paper, demonstrated that RapidArc can compete with the IMRT technique in the field of treatment plan dosimetry reducing the time required for dose delivery.     

Biogeographical patterns and Rapoport's rule in southeastern Pacific benthic polychaetes of the Chilean coast

Recently three biogeographical units were identified along the Chilean coast (the Magellanic Province, an Intermediate Area, and the Peruvian Province), however few studies have focused on the factors and dynamic processes that formed these spatial units (e.g. Rapoport's rule and its causal mechanisms). In this study we used benthic polychaetes of the Chilean coast to evaluate patterns of latitudinal distribution and species richness, and the existence of the three main biogeographical provinces described for the Chilean coast. Additionally, we evaluated the latitudinal Rapoport effects and geometric constraint as a null hypothesis explaining the species richness distribution.
We found that benthic polychaete diversity increased towards southern latitudes. The cluster and ordination (non-metric MultiDimensional Scaling, nMDS) analyses of the distribution data, presented only two statistically significant (bootstrapping techniques) biogeographic provinces along the Chilean coast, with a break occurring between 41° and 42°S. While, our results did not support a latitudinal Rapoport effect, they did support the view that latitudinal Rapoport effects are a local phenomenon, occurring only for the Northeastern Pacific marine taxa. The relationship between latitudinal range extent and mean latitude indicated the existence of two hard boundaries at either extreme of the Chilean coast, limiting the geographical ranges of the species. However, geometric constraints tested using a Monte Carlo simulation approach showed a weak level of mid-domain effect on species richness. Finally, we propose that geometric constraint together with the geomorphology and historical characteristics of the Chilean coast explain the biogeographical patterns of benthic polychaete taxa in Chile.     

The influence of hypomagnesemia on erythrocyte antioxidant enzyme defence system in mice

The effect of magnesium deficiency on antioxidant defence system was studied in RBC of mice suffering from hypomagnesemia. The animals were kept for 8, 15 and 22 days on magnesium-deficient diet with consequent reduction of magnesium level in plasma by 38% at the first 8 days and by 64% after 22 days of experiment. The activities of the most important antioxidant enzymes, catalase, glutathione peroxidase, superoxide dismutase, glutathione reductase, glutahione S-transferase were assayed in hemolysates. The level of reduced glutathione in erythrocytes was measured as well. Apart from catalase, the activities of antioxidant enzymes were decreasing. The activity of superoxide dismutase decreased gradually during the experiment and on the 15th and 22nd day of experiment was significantly (P<0,05) lowered by 30 and 32% respectively. The catalase activity was increased on each point of the experiment with the peak value up to 149% on 15th day, and by 32% on 22nd day. Glutathione peroxidase activity was insignificantly reduced. The reduction of Glutatione reductase and Glutathione S-transferase activities by 24 and 21%, respectively, were observed after 8 days of the experiment with a further downward tendency. The reduced glutathione was significantly depleted after 8 days by 33% and was kept on that level in the course of the study. These findings support previous reports on the hypomagnesemia – induced alteration in endogenous enzyme antioxidant defences and glutathione redox cycle of mice.